Giachino Daniela, van Duist Marjan Maria, Regazzoni Silvia, Gregori Dario, Bardessono Marco, Salacone Paola, Scaglione Nadia, Sostegni Raffaello, Sapone Nicoletta, Bresso Francesca, Sambataro Angela, Gaia Ezio, Pera Angelo, Astegiano Marco, De Marchi M
Department of Clinical and Biological Sciences, University of Torino, Italy.
Eur J Hum Genet. 2004 Mar;12(3):206-12. doi: 10.1038/sj.ejhg.5201130.
CARD15 on chromosome 16 is the only IBD susceptibility gene identified among several mapped loci. Its recurrent variants R702W, G908R and L1007fs have shown significant association with Crohn's disease (CD), but not with ulcerative colitis (UC), in different Caucasian populations. We analysed these three variants in 184 CD and 92 UC Italian patients and in 177 healthy controls. L1007fs and G908R were independently associated with CD, while R702W showed a nonsignificant increase. After combining the three variants together, 32.6% of CD patients were positive vs 18.6% of the controls. The association was stronger for homozygotes and compound heterozygotes, OR 13.9 (1.8-108), and weaker but still significant for simple heterozygotes, OR 1.7 (1.0-2.9). An excess of homozygotes/compound heterozygotes also resulted from the comparison with Hardy-Weinberg expectations. Phenotype-genotype correlations were analysed first by univariate logistic regression and then by multivariate analysis, the effect of CARD15 positivity being adjusted according to the status of smoking, familiarity and sex, so as to focus on the predictivity of genetic and environmental risk factors on the clinical phenotype. Significant risk estimates of the CARD15 genotype were obtained for stricturing vs inflammatory behaviour, OR 2.76 (1.2-6.3), and for penetrating behaviour, 2.59 (1.0-6.6), and marginally significant for ileal vs colic location, OR 3.0 (0.9-9.8). Our findings indicate that the association of the CARD15 genotype with behaviour and location of disease holds also for the Italian population.
位于16号染色体上的CARD15是在多个已定位基因座中鉴定出的唯一IBD易感基因。在不同的白种人群中，其常见变异体R702W、G908R和L1007fs与克罗恩病（CD）显著相关，但与溃疡性结肠炎（UC）无关。我们对184例意大利CD患者、92例意大利UC患者以及177名健康对照者的这三种变异体进行了分析。L1007fs和G908R分别与CD独立相关，而R702W的相关性不显著。将这三种变异体合并分析后，32.6%的CD患者呈阳性，而对照组为18.6%。纯合子和复合杂合子的关联更强，比值比（OR）为13.9（1.8 - 108），单纯杂合子的关联较弱但仍显著，OR为1.7（1.0 - 2.9）。与哈迪-温伯格预期值相比，纯合子/复合杂合子也出现了过剩。首先通过单因素逻辑回归分析表型-基因型相关性，然后进行多因素分析，根据吸烟状况、家族史和性别对CARD15阳性的影响进行校正，以便重点关注遗传和环境风险因素对临床表型的预测性。对于狭窄型与炎症型表现，CARD15基因型的显著风险估计值为OR 2.76（1.2 - 6.3），对于穿透型表现为2.59（1.0 - 6.6），对于回肠病变与结肠病变部位，OR为3.0（0.9 - 9.8），具有边缘显著性。我们的研究结果表明，CARD15基因型与疾病表现及部位的关联在意大利人群中同样成立。
